Tricyclic Marine Alkaloids: Synthetic Approaches to Cylindricines, Lepadiformine, and Fasicularin

Schär, Pascal; Cren, Sylvaine; Renaud, Philippe

doi:10.2533/000942906777674976

“…For example, the n ‐hexyl adduct (Table 3, entry 4) is a precursor for the formal asymmetric synthesis of lepadiformine 21. 22 Other useful transformations can be envisioned on the exocyclic double bond, such as oxidation to a ketone or selective epoxidation.…”

Section: Methodsmentioning

confidence: 99%

β‐Disubstituted Allylic Chlorides: Substrates for the Cu‐Catalyzed Asymmetric S_N2′ Reaction

Falciola

¹

,

Tissot-Croset

²

,

Alexakis

³

2006

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Metal-promoted asymmetric catalysis has proven to be an efficient method in carbon-carbon bond-forming reactions to obtain optically enriched compounds. Allylic substitution has attracted much attention and great effort has been put into controlling the chemo-, regio-, and enantioselective outcome of the reaction.[1] Extensive accounts report a wide variety of metals that use soft nucleophiles for the reaction (Pd, Ir, Mo, Rh, Ru).[2] In contrast, copper allows the use of hard, nonstabilized nucleophiles, such as small alkyl groups in the form of organometallic species.[3] Among the broad range of reagents available, the use of Grignard reagents in the catalyzed asymmetric allylic substitution reaction was first reported by Bäckvall et al., [4] with chiral copper thiolates yielding moderate ee values. This pioneering work was soon followed by a report from Dübner and Knochel, [5] who disclosed a different system based on diorganozinc reagents. Other ligands have been introduced for the stereoselective allylic addition of organomagnesium reagents, such as chiral diaminocarbenes by Okamoto et al., [6] and more recently ferrocenic bidentate phosphines by Feringa et al. [7] In the past few years, our group has reported highly regioand enantioselective Cu-phosphoramidite catalytic reactions for the substitution of allylic chlorides by organomagnesium reagents. [8] This methodology was applied, in particular, to the formal synthesis of profen molecules by the highly efficient and valuable stereoselective allylic addition of MeMgBr with ee values up to 96 %.[9] Subsequently, we focused on the application of our procedure to diverse substrates, and report herein the unprecedented Cu-catalyzed asymmetric allylic alkylation of b-disubstituted allylic halides.The Cu-catalyzed asymmetric S N 2' reaction has mostly been limited to disubstituted olefinic systems. [10,11] Type A substrates (Scheme 1) that lead to chiral quaternary centers through catalytic allylic alkylation are scarcely documented, with the exception of reports from Hoveyda and co-workers who reached excellent enantioselectivities on g-disubstituted allylic phosphates. [12,13] Other than the results reported by Woodward and co-workers on the stereoselective addition to Baylis-Hillman-derived allylic electrophiles, [14] copper-catalyzed asymmetric allylic alkylation on type B substrates, the b-disubstituted olefinic system, has not previously been described.Preliminary experiments for this study started with a short screening of biphenol- [15] and binaphthol-based [8b, 16] phosphoramidite ligands (Scheme 2) on trans-(3-chloro-2-methylprop-1-enyl)benzene (1), the b-methylcinnamyl chloride (Scheme 3). The results are summarized in Table 1. The allylic substitution of 1 by the slow addition of ethylmagnesium bromide, catalyzed by copper thiophene carboxylate (CuTC; 1 mol %) and different phosphoramidite ligands (1.1 mol %), gave adducts with poor-to-good g/a ratios and provided high enantiomeric excess up to 96 % ee with ligand L6 (Table 1, entry 6).Interesting...

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“…The 6-azaspiro [4,5]decane structures of halichlorine 4 and pinnaic acid 7 are even more impressive than their bioactivities. They have attracted considerable attention in the synthetic chemistry community and have recently been the topic of a specific review and a large number of reports describing efforts to synthesize them.…”

Section: Total Syntheses Of Halichlorine and Pinnaic Acidmentioning

confidence: 99%

“…Lithiation of 27 followed by treatment of the lithiated allyl sulfoximines with 2.1 equivalents of ClTi(Oi-Pr) 3 furnished the corresponding bis(allyl)titanium complexes admixed with ClTi(Oi-Pr) 3 and Ti(Oi-Pr) 4 . This mixture was reacted with acetaldehyde in high regioselectivity (≥95%) and good diastereoselectivity (74-84% de) at the γ-position to afford homoallylic alcohols 28 and 36 (Table 2).…”

Section: Application Of the Hydroxyalkylation Reaction To The Synthesmentioning

confidence: 99%

“…Then the mixture was allowed to warm to room temperature within 12 h. Saturated aqueous NH 4 Cl (50 mL Melting point: 148 °C (decomposition).…”

Section: Intramolecular Aza-michael Addition 241 (4r4as7ar)-4-metmentioning

confidence: 99%

“…Cylindricine A 6 and lepadiformine 3 ( Figure 5) are marine alkaloids with a common novel pyrroloquinoline skeleton. 4,5 The cylindricines were isolated from the marine ascidian Clavelina cylindrica by BLACKMAN and co-workers between 1993 and 1995. Cylindricine A 6, for example, showed some biological activity in the brine shrimp assay.…”

Section: Introduction To Azaspirocycles and Aims Of The Projectmentioning

confidence: 99%

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Modular Asymmetric Synthesis of Functionalized Azaspirocycles Based on the Sulfoximine Auxiliary

Adrien

¹

,

Gais

²

,

Köhler

³

et al. 2007

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A modular asymmetric synthesis of the functionalized azaspirocycles 6 (m = 2, n = 1), 7 (m = 1, n = 2), 8 (m = n = 2), 12, 20, and 24 from the cyclic allylic sulfoximines 1 is described. The synthetic strategy is based on the stereoselective construction of the carbocycle 4 containing the amino-substituted tertiary C atom from 1 followed by the generation of the azaspirocycle. Three different routes have been followed for the synthesis of the heterocyclic ring: N,C-dianion cycloalkylation, ring-closing metathesis, and N-acyl iminium ion formation.

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Ascidians (Tunicates)–2

Kornprobst

¹

2014

Encyclopedia of Marine Natural Products

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The article contains sections titled: Metabolites of Polyclinidae Long‐Chain Sulfated Alkanes and Terpenes of Sidnyum turbinatum Terpenes and Meroterpenes Para‐ and Metacyclophanes: Longithorones and Related Derivatives Simple Aromatic Derivatives Nitrogenous and Non‐Nitrogenous Macrolides Long‐Chain Amines and Amino Alcohols, Sphingosines Piperidine Alkaloids: Pseudodistomins Indole and β‐Carboline Alkaloids Quinoline and Pyridoacridine Alkaloids Bis‐Steroidal Alkaloids of Ritterella tokioka : Ritterazines Purines and Nucleosides Miscellaneous Nitrogenous Derivatives Metabolites of Ascidiidae Vanadium, Intracellular Acidity of Blood Cells, and Peptide Ligands Metabolites of Cionidae Metabolites of Diazonidae Metabolites of Perophoridae Metabolites Isolated from Species of the Genus Perophora Tetrahydroisoquinoline Alkaloids: Ecteinascidins Metabolites of Molgulidae and Pyuridae Lipids and Non‐Nitrogenous Derivatives Nitrogenous Derivatives, Antimicrobial Peptides, and Proteins Metabolites of Styelidae Non‐Nitrogenous Derivatives Phenylethylamine Derivatives, Various Alkaloids Antibacterial Purines and Peptides

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Tricyclic Marine Alkaloids: Synthetic Approaches to Cylindricines, Lepadiformine, and Fasicularin

Cited by 33 publications

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β‐Disubstituted Allylic Chlorides: Substrates for the Cu‐Catalyzed Asymmetric S_N2′ Reaction

β‐Disubstituted Allylic Chlorides: Substrates for the Cu‐Catalyzed Asymmetric S_N2′ Reaction

Modular Asymmetric Synthesis of Functionalized Azaspirocycles Based on the Sulfoximine Auxiliary

Ascidians (Tunicates)–2

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Tricyclic Marine Alkaloids: Synthetic Approaches to Cylindricines, Lepadiformine, and Fasicularin

Cited by 33 publications

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β‐Disubstituted Allylic Chlorides: Substrates for the Cu‐Catalyzed Asymmetric SN2′ Reaction

β‐Disubstituted Allylic Chlorides: Substrates for the Cu‐Catalyzed Asymmetric SN2′ Reaction

Modular Asymmetric Synthesis of Functionalized Azaspirocycles Based on the Sulfoximine Auxiliary

Ascidians (Tunicates)–2

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Product

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β‐Disubstituted Allylic Chlorides: Substrates for the Cu‐Catalyzed Asymmetric S_N2′ Reaction

β‐Disubstituted Allylic Chlorides: Substrates for the Cu‐Catalyzed Asymmetric S_N2′ Reaction